Hybrid ion mobility spectrometer

ABSTRACT

A hybrid ion mobility spectrometer includes a single-pass drift tube having an ion inlet at one end and an ion outlet at an opposite end, a multiple-pass drift tube having an ion inlet and an ion outlet each coupled to the single pass drift tube between the ion inlet and the ion outlet thereof, and a set of ion gates each controllable between an open position to pass ions therethrough and a closed position to block ions from passing therethrough. The set of ion gates may be controlled to pass at least some ions traveling through the single-pass drift tube into the multiple-pass drift tube via the ion inlet of the multiple-pass drift tube and to pass at least some ions traveling through the multiple-pass drift tube into the single-pass drift tube via the ion outlet of the multiple-pass drift tube.

CROSS-REFERENCE TO RELATED APPLICATION

This patent application claims the benefit of, and priority to, U.S.Patent Application Ser. No. 61/882,891, filed Sep. 26, 2013, thedisclosure of which is incorporated herein by reference in its entirety.

GOVERNMENT RIGHTS

This invention was made with government support under GM090797 awardedby the National Institutes of Health. The United States Government hascertain rights in the invention.

FIELD OF THE INVENTION

This disclosure relates generally to the field of spectrometry, and morespecifically to instruments for separating ions in time as a function ofion mobility.

BACKGROUND

Ion mobility spectrometers are analytical instruments used toinvestigate properties of charged particles by separating the chargedparticles, i.e., ions, in time as a function of ion mobility. In thetypical ion mobility spectrometers, an electric drift field isestablished in a drift tube filled with a buffer gas, and as the ionsmove through the drift tube under the influence of the electric driftfield the ions collide with the buffer gas and separate as a functiontheir collision cross-sections such that more compact conformers reachthe end of the drift tube faster than less compact conformers. Knowndrift tubes may be so-called single-pass drift tubes, i.e., linear ornon-linear drift tubes through which ions traverse only once between ioninlets and outlets thereof, or so-called multiple-pass drift tubes,i.e., linear or closed-path drift tubes through which ions may traversemultiple times before exit.

SUMMARY

The present invention may comprise one or more of the features recitedin the attached claims, and/or one or more of the following features andcombinations thereof. A hybrid ion mobility spectrometer may comprise asingle-pass drift tube having an ion inlet at one end and an ion outletat an opposite end, a multiple-pass drift tube having an ion inlet andan ion outlet each coupled to the single pass drift tube between the ioninlet of the single-pass drift tube and the ion outlet of thesingle-pass drift tube, and a set of ion gates each controllable betweenan open position to pass ions therethrough and a closed position toblock ions from passing therethrough. The set of ion gates may becontrolled between the open and closed positions to selectively pass atleast some of the ions traveling through the single-pass drift tube intothe multiple-pass drift tube via the ion inlet of the multiple-passdrift tube and to selectively pass at least some of the ions travelingthrough the multiple-pass drift tube into the single-pass drift tube viathe ion outlet of the multiple-pass drift tube. The single-pass drifttube may be configured to separate in time ions entering the ion inletthereof and traveling therethrough according to a first function of ionmobility, and the multiple-pass drift tube may be configured to separatein time ions entering the ion inlet thereof and traveling one or moretimes therethrough according to the first or a second function of ionmobility.

Each of the set of ions gates may be controllable to the open positionin response to a different first ion gate control signal andcontrollable to the closed position in response to a different secondion gate control signal. The hybrid ion mobility spectrometer in thisembodiment may further comprise a first plurality of voltage sources toproduce the different first and second ion gate control signals. One ormore voltage sources within the first plurality of voltage sources maybe programmable to control timing of production of at least one of thedifferent first ion gate control signals and at least one of thedifferent second ion gate control signals. The hybrid ion mobilityspectrometer may further or alternatively comprise a processorelectrically coupled to at least one of the first plurality of voltagesources, and the processor may be configured to control timing ofproduction of at least one of the different first ion gate controlsignals and at least one of the different second ion gate controlsignals.

The single-pass drift tube in any of the preceding paragraphs may beresponsive to a first set of voltage signals to separate ions in timeaccording to the first function of ion mobility and the multiple-passdrift tube may be responsive to a second set of voltage signals toseparate ions in time according to the first or second function of ionmobility, and the hybrid ion mobility spectrometer may further comprisea second plurality of voltage sources to produce the first and secondsets of voltage signals. In one embodiment, one or more voltage sourceswithin the second plurality of voltage sources may be programmable tocontrol production of at least one of the first and second sets ofvoltage signals. Alternatively or additionally, the ion mobilityspectrometer may further comprise a processor electrically coupled to atleast one of the second plurality of voltage sources, and the processormay be configured to control production of at least one of the first andsecond sets of voltage signals.

In the hybrid ion mobility spectrometer of any of the precedingparagraphs, each of the set of ion gates may be controllable to at leastone intermediate position to pass at least some ions therethrough. Oneor more of the set of ion gates may be controlled to the at least oneintermediate position to selectively pass some of the ions travelingthrough the single-pass drift tube into the multiple-pass drift tubewhile also allowing others of the ions traveling through the single-passdrift to travel through the single-pass drift tube to the outletthereof.

In the hybrid ion mobility spectrometer of any of the first threeparagraphs of this SUMMARY section, the set of ions gates may define afirst combination of open and closed positions of the gates within theset of ion gates that directs ions to travel through the single-passdrift tube while blocking ions from entering the ion inlet of themultiple-pass drift tube, such that ions entering the ion inlet of thesingle-pass drift tube travel completely through the single-pass drifttube and exit the ion outlet thereof, a second combination of open andclosed positions of the gates within the set of ion gates that directsat least some of the ions traveling through the single-pass drift tubeinto the ion inlet of the multiple-pass drift tube, a third combinationof open and closed positions of the ion gates within the set of iongates that directs ions in the multiple-pass drift tube to travelmultiple times therethrough while blocking ions traveling through themultiple-pass drift tube from exiting the ion outlet thereof andre-entering the single-pass drift tube, and a fourth combination of openand closed positions of the ion gates within the set of ion gates thatdirects at least some of the ions traveling through the multiple-passdrift tube through the ion outlet thereof and into the single-pass drifttube, such that ions entering the single-pass drift tube from the ionoutlet of the multiple-pass drift tube travel toward and exit throughthe ion outlet of the single-pass drift tube.

In the hybrid ion mobility spectrometer of any of the precedingparagraphs, the multiple-pass drift tube may comprise a closed-pathdrift tube, the ion inlet of the multiple-pass drift tube may comprisean ion inlet tube having an ion outlet integrally formed with themultiple-pass drift tube and the ion outlet of the multiple-pass drifttube may comprise an ion outlet tube having an ion inlet integrallyformed with the multiple-pass drift tube. Illustratively, a portion ofthe single-pass drift tube may be integral with the closed-path drifttube. The single-pass drift tube may, for example, comprise a firstplurality of cascaded drift tube segments, the closed-path drift tubemay comprise a second plurality of cascaded drift tube segments with anion outlet of a last one of the second plurality of cascaded drift tubesegments coupled to an ion inlet of a first one of the second pluralityof cascaded drift tube segments, and at least one of the first pluralityof drift tube segments and at least one of the second plurality of drifttube segments may define at least one common drift tube segment. The ioninlet tube of the multiple-pass drift tube may have an ion inlet coupledto an ion outlet of one of the first plurality of drift tube segments ofthe single-pass drift tube between the ion inlet of the single-passdrift tube and the ion outlet of the single-pass drift tube, and the ionoutlet tube of the multiple-pass drift tube may have an ion outletcoupled to an ion inlet of another of the first plurality of drift tubesegments of the single-pass drift tube between the one of the firstplurality of drift tube segments of the single-pass drift tube and theion outlet of the single-pass drift tube. The single-pass drift tube inthis embodiment is thereby defined by a cascaded arrangement of a firstsubset of the first plurality of drift tube segments between the ioninlet of the single-pass drift tube and the ion outlet of the one of thefirst plurality of drift tube segments, the ion inlet tube of themultiple-pass drift tube, at least one of the second plurality of drifttube segments of the closed-path drift tube, the ion outlet tube of themultiple-pass drift tube and at least one of the first plurality ofdrift tube segments between the another of the first plurality of drifttube segments and the ion outlet of the single-pass drift tube. In thisembodiment, the set of ion gates may comprise a first ion gatecontrollable between the open position to direct ions in themultiple-pass drift tube about the closed-path drift tube and a closedposition to block ions in the multiple-pass drift tube from travelingabout the closed-path drift tube, and a second ion gate controllablebetween the closed position to block ions traveling about theclosed-path drift tube from exiting the closed-path drift tube via theion outlet tube of the multiple-pass drift tube and the open position todirect ions traveling about the closed-path drift tube through the ionoutlet tube of the multiple-pass drift tube and into the single-passdrift tube. The set of ion gates may further comprise a third ion gatecontrollable between the open position to direct ions in the single-passdrift tube into the closed-path drift tube and a closed position toblock ions in the single-pass drift tube from entering the closed-pathdrift tube.

In other embodiments in which the multiple-pass drift tube may comprisea closed-path drift tube, the ion inlet of the multiple-pass drift tubemay comprise an ion inlet tube having an ion outlet integrally formedwith the multiple-pass drift tube and the ion outlet of themultiple-pass drift tube may comprise an ion outlet tube having an ioninlet integrally formed with the multiple-pass drift tube, thesingle-pass drift tube may comprise a first plurality of linearlyarranged, cascaded drift tube segments, the closed-path drift tube maycomprise a second plurality of cascaded drift tube segments with an ionoutlet of a last one of the second plurality of cascaded drift tubesegments coupled to an ion inlet of a first one of the second pluralityof cascaded drift tube segments, and the ion inlet of the multiple-passdrift tube may be coupled to one of the first plurality of drift tubesegments and the ion outlet of the multiple-pass drift tube may becoupled to another of the first plurality of drift tube segmentsdownstream of the one of the first plurality of drift tube segments. Inthis embodiment, the ion inlet tube of the multiple-pass drift tube mayhave an ion inlet coupled to a first ion outlet of the one of the firstplurality of drift tube segments of the single-pass drift tube, the oneof the first plurality of drift tube segments of the single-pass drifttube may have a second ion outlet coupled to an ion inlet of a next oneof the first plurality of drift tube segments, the ion outlet tube ofthe multiple-pass drift tube may have an ion outlet coupled to a firstion inlet of the another of the first plurality of drift tube segmentsof the single-pass drift tube, and the another of the first plurality ofdrift tube segments may have a second ion inlet coupled to an ion outletof a previous one of the first plurality of drift tube segments that isdownstream of the next one of the first plurality of drift tubesegments. Further in this embodiment, the set of ion gates may comprisea first ion gate controllable between the open position to direct ionsin the one of the first plurality of drift tube segments of thesingle-pass drift tube through the first ion outlet thereof and into theion inlet tube of the multiple-pass drift tube and the closed positionto block ions in the one of the first plurality of drift tube segmentsof the single-pass drift tube from passing through the first ion outletthereof and entering the ion inlet tube of the multiple-pass drift tube,and a second ion gate controllable between the open position to directions in the one of the first plurality of drift tube segments of thesingle-pass drift tube through the second ion outlet thereof and intothe ion inlet of the next one of the first plurality of drift tubesegments and the closed position to block ions in the one of the firstplurality of drift tube segments of the single-pass drift tube frompassing through the second ion outlet thereof and entering the ion inletof the next one of the first plurality of drift tube segments. The setof ion gates in this embodiment may further comprise a third ion gatecontrollable between the open position to direct ions in themultiple-pass drift tube about the closed-path drift tube and a closedposition to block ions in the multiple-pass drift tube from travelingabout the closed-path drift tube, and a fourth ion gate controllablebetween the closed position to block ions traveling about theclosed-path drift tube from exiting the closed-path drift tube via theion outlet tube of the multiple-pass drift tube and the open position todirect ions traveling about the closed-path drift tube through the ionoutlet tube of the multiple-pass drift tube and into the single-passdrift tube.

In the hybrid ion mobility spectrometer of any of the first fourparagraphs of this SUMMARY section, the single-pass drift tube mayalternatively comprise a first plurality of linearly arranged, cascadeddrift tube segments, the multiple-pass drift tube may comprise aclosed-path drift tube, with the closed-path drift tube comprising asecond plurality of cascaded drift tube segments with an ion outlet of alast one of the second plurality of cascaded drift tube segments coupledto an ion inlet of a first one of the second plurality of cascaded drifttube segments, and the ion inlet and the ion outlet of the multiple-passdrift tube may together comprise an ion inlet-outlet tube coupled at oneend to one of the first plurality of drift tube segments between the ioninlet of the single-pass drift tube and the ion outlet of thesingle-pass drift tube and at an opposite end to one of the secondplurality of drift tube segments. The set of ion gates in thisembodiment may comprise a first ion gate controllable between the openposition to direct ions in the one of the first plurality of drift tubesegments of the single-pass drift tube therethrough and into an ioninlet of a next one of the first plurality of drift tube segments andthe closed position to block ions in the one of the first plurality ofdrift tube segments of the single-pass drift tube from passingtherethrough and entering the ion inlet of the next one of the firstplurality of drift tube segments, and a second ion gate controllablebetween the open position to direct ions in the one of the firstplurality of drift tube segments therethrough and into the ioninlet-outlet tube or to direct ions in the ion inlet-outlet tubetherethrough and into the one of the first plurality of drift tubesegments, and a closed position to block ions in the first one of theplurality of drift tube segments from passing therethrough and enteringthe ion inlet-outlet tube or to block ions in the ion inlet-outlet tubefrom passing therethrough and entering the one of the first plurality ofdrift tube segments. The set of ion gates may further comprise a thirdion gate controllable between the open position to direct ions in theion inlet-outlet tube therethrough and into the closed-path drift tubeor to direct ions in the closed-path drift tube therethrough and intothe ion inlet-outlet tube, and the closed position to block ions in theion inlet-outlet tube from passing therethrough and entering theclosed-path drift tube or to block ions in the closed-path drift tubefrom passing therethrough and entering the ion inlet-outlet tube, and afourth ion gate controllable between the open position to direct ions inthe multiple-pass drift tube about the closed-path drift tube and aclosed position to block ions in the multiple-pass drift tube fromtraveling about the closed-path drift tube.

The hybrid ion mobility spectrometer of any of the preceding paragraphsmay further comprise an ion source coupled to the ion inlet of thesingle-pass drift tube, the ion source configured to generate ions froma sample.

The hybrid ion mobility spectrometer of any of the preceding paragraphsmay further comprise an ion detector to detect ions exiting the ionoutlet of the single-pass drift tube and to produce an ion detectionsignal corresponding thereto. The hybrid ion mobility spectrometer inthis embodiment may further comprise a processor to process the iondetection signal and produce corresponding ion mobility spectralinformation as a function of ion drift time.

A method for separating ions may comprise introducing ions into an ioninlet of a first drift tube, establishing at least a first electricfield within the first drift tube to cause the ions introduced into theion inlet thereof to travel through the first drift tube from the ioninlet thereof toward an ion outlet thereof while separating in timeaccording to a first function of ion mobility, controlling a set of iongates to direct at least some of the ions traveling through the firstdrift tube into a second drift tube via an ion inlet of the second drifttube that is coupled to the first drift tube between the ion inlet ofthe first drift tube and the ion outlet of the first drift tube,establishing at least a second electric field within the second drifttube to cause ions entering the ion inlet thereof to travel through thesecond drift tube while separating in time according to the first or asecond function of ion mobility, controlling the set of ion gates tocause ions traveling through the second drift tube to travel through thesecond drift tube multiple times, and controlling the set of ion gatesto direct at least some of the ions having traveled the multiple timesthrough the second drift tube into the first drift tube via an ionoutlet of the second drift tube that is coupled to the first drift tubebetween the ion inlet of the first drift tube and the ion outlet of thefirst drift tube, wherein at least some of the ions passing into thefirst drift tube from the ion outlet of the second drift tube traveltoward and exit through the ion outlet of the first drift tube.

Introducing ions into the ion inlet of the first drift tube may compriseintroducing a first set of ions into the ion inlet of the first drifttube, and the method may further comprise controlling the set of iongates to cause the first set of ions to travel through the first drifttube and exit through the ion outlet the first drift tube, determining,based on the first set of ions exiting the ion outlet of the first drifttube, a range of ion mobilities of at least some of the first set ofions, and introducing a second set of ions into the ion inlet of thefirst drift tube after introducing the first set of ions into the ioninlet of the first drift tube. Controlling the set of ion gates todirect at least some of the ions traveling through the first drift tubeinto the second drift tube in this embodiment may comprise controllingthe set of ion gates to direct the second set of ions traveling throughfirst drift tube into the second drift tube via the ion inlet of thesecond drift tube, and the method may further comprise controlling thesecond electric field to cause only ions in the second set of ions thatare within the determined range of ion mobilities to travel through thesecond drift tube. Controlling the set of ion gates to direct at leastsome of the ions having traveled the multiple times through the seconddrift tube into the first drift tube may then illustratively comprisecontrolling the set of ion gates to direct ions from the second set ofions that are traveling through the second drift tube into the firstdrift tube via the ion outlet of the second drift tube, and the ionsfrom the second set of ions passing into the first drift tube from theion outlet of the second drift tube may exit through the ion outlet ofthe first drift tube and have ion mobilities only within the determinedrange of ion mobilities. The method may further comprise generating thefirst and second sets of ions from a common sample.

The second drift tube may comprise a number of cascaded drift tubesegments, and controlling the second electric field to cause only ionsin the second set of ions that are within the range of ion mobilities totravel through the second drift tube may comprise sequentiallyestablishing and disestablishing the second electric field within thecascaded drift tube segments at a rate that corresponds to drift timesassociated with the range of ion mobilities.

The second drift tube may define a closed path, the ion inlet of thesecond drift tube comprises an ion inlet tube integrally formed with thesecond drift tube and the ion outlet of the second drift tube comprisesan ion outlet tube also integrally formed with the second drift tube,and controlling the set of ion gates to cause ions traveling through thesecond drift tube to travel through the second drift tube multiple timesmay comprise controlling the set of ion gates to block the ionstraveling through the second drift tube from exiting the second drifttube via the ion outlet of the second drift tube and to direct the ionstraveling through the second drift tube to travel multiple times aboutthe closed path.

One or more of the steps of controlling the set of ion gates maycomprise controlling the set of ion gates using a processor.

An ion detector may detect ions exiting the ion outlet of the firstdrift tube and produce an ion detection signal corresponding thereto,and the method may further comprise processing the ion detection signalto produce ion mobility spectral information as a function of ion drifttime.

The method may further comprise generating ions prior to introducing theions into the ion inlet of the first drift tube.

The method may further comprise clearing the first drift tube of ionsafter introducing the first set of ions into the ion inlet of the firstdrift tube and before introducing the second set of ions into the ioninlet of the second drift tube.

A plurality of voltage sources may each be operatively connected to oneor more of the ion gates in the set of ion gates, and each of the iongates in the set of ion gates may be controllable between an openposition to pass ions therethrough and a closed position to block ionsfrom passing therethrough. Each of the ion gates in the set of ionsgates may be responsive to a first voltage applied thereto to open tothe open position and to a second voltage applied thereto to close tothe closed position. One or more of the steps of controlling the set ofion gates may comprise controlling voltages produced by one or more ofthe plurality of voltage sources to selectively control one or more ofthe ion gates in the set of ion gates to the open or closed position.The voltage produced by the one or more of the plurality of voltagesources may be programmable, wherein controlling voltages produced bythe one or more of the plurality of voltage sources may compriseprogramming the one or more of the plurality of voltage sources tocontrol the timing of production of the first and/or second voltages, ora processor may be operatively connected to the one or more of theplurality of voltage sources, and controlling voltages produced by theone or more of the plurality of voltage sources may comprise controllingvia the processor the timing of production of the first and/or secondvoltages.

Controlling the set of ion gates to direct at least some of the ionstraveling through the first drift tube into the second drift tube may,in some embodiments, comprise controlling the set of ion gates to directsome of the ions traveling through the first drift tube into the seconddrift tube while also allowing others of the ions traveling through thefirst drift to travel through the first drift tube to the outletthereof. In such embodiments, introducing ions into the ion inlet of thefirst drift tube may comprise continually introducing ions into the ioninlet of the first drift tube. Alternatively, introducing ions into theion inlet of the first drift tube may comprise intermittently orperiodically introducing ions into the ion inlet of the first drifttube.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a simplified diagram of an embodiment of a hybrid ionmobility spectrometer.

FIG. 1B is a simplified diagram of an alternate embodiment of a hybridion mobility spectrometer,

FIG. 1C is a simplified diagram of another alternate embodiment of ahybrid ion mobility spectrometer.

FIG. 1D is a simplified diagram of yet another alternate embodiment of ahybrid ion mobility spectrometer.

FIG. 1E is a simplified diagram of the embodiment illustrated in FIG. 1Dviewed orthogonally from the view illustrated in FIG. 1D.

FIG. 1F is a simplified diagram of an embodiment of the transitionregion of the hybrid ion mobility spectrometer illustrated in FIGS. 1Dand 1E.

FIG. 2 is a simplified diagram of an embodiment of a drift tube segmentthat may be used in any of the hybrid ion mobility spectrometers ofFIGS. 1A-1C.

FIG. 3 includes FIGS. 3A and 3B and is a simplified flowchart of anembodiment of a process for separating ions using any of the hybrid ionmobility spectrometers of FIGS. 1A-1F.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to a number of illustrativeembodiments shown in the attached drawing and specific language will beused to describe the same.

Referring to FIG. 1A, a simplified diagram of an embodiment of a hybridmobility spectrometer 10 is shown. The hybrid ion mobility spectrometer10 illustratively includes a single-pass drift tube 12 through whichions can be separated in time according to a first function of ionmobility, and a multiple-pass drift tube 14, coupled to the single-passdrift tube 12 between an ion inlet 16 and an ion outlet 20 of thesingle-pass drift tube 12, through which ions can be separated in timeaccording to a second function of ion mobility. The spectrometer 10further illustratively includes a set of ion gates, e.g., G1-G3, each ofwhich are controllable between open and closed positions, and the set ofion gates is illustratively controlled such that some or all of the ionstraveling through the single-pass drift tube 12 may be selectivelypassed into the multiple-pass drift tube 14 via an ion inlet 36 ₁ of themultiple-pass drift tube 14, and some or all of the ions travelingthrough the multiple-pass drift tube 14 may be selectively passed backinto the single-pass drift tube 12 via an ion outlet 36 ₂ of themultiple-pass drift tube 14, and the ions then exit the single-passdrift tube 12 via the ion outlet 20 thereof. In the embodimentillustrated in FIG. 1A, an ion source 18 is coupled to the ion inlet 16of the single-pass drift tube 12, and an ion detector 22 is positionedto receive ions exiting the ion outlet 20 of the single-pass drift tube12.

The foregoing configuration of the ion mobility spectrometer 10 providesfor the ability to pass all or a subset of ions in the single-pass drifttube 12 to the multiple-pass drift tube 14 for additional and/oralternate separation before the ions exit the outlet 20 of thesingle-pass drift tube 12. Advantageously, because both drift tubes 12,14 operate on ions generated from a single ion source 18 coupled to theion inlet 16 of the single-pass drift tube 12, such additional and/oralternate separation may thus be carried out using ions from the samesample. In one specific operational mode of the hybrid ion mobilityspectrometer 10 illustrated in FIG. 1A, for example, the set of iongates, e.g., ion gates G1-G3, may be controlled such that ions generatedby the ion source 18 are first confined to the single-pass drift tube12, and electric fields within the single-pass drift tube 12 arecontrolled such that ions generated at the ion source 18 travel, i.e.,drift, through only the single-pass drift tube 12 where they separate intime as a first function of ion mobility defined by the variousstructural dimensions and operating parameters of the single-pass drifttube 12. The resulting ion spectral information is then analyzed and if,for example, it is discovered that in the ion spectral information asubset, e.g., two or more, of ion intensity peaks in an ion mobilityrange of interest, e.g., in a particular range of drift times, arecrowded together and cannot be satisfactorily resolved over the lengthof the single-pass drift tube 12, ions are then generated a second time,or are continuously generated without interruption, and the set of iongates, e.g., ion gates G1-G3, is controlled in one embodiment to pass ordivert ions traveling through the single-pass drift tube 12 that arewithin the ion mobility range of interest into the multiple-pass drifttube 14. The set of ion gates, e.g., ion gates G1-G3, is then controlledto confine the diverted ions within the multiple-pass drift tube 14 andelectric fields within the multiple-pass drift tube 14 are controlledsuch that the diverted ions pass, i.e., drift, one or more timesthrough, i.e., about, the multiple-pass drift tube 14 and separate intime according to a second function of ion mobility, which may or maynot be the same as the first function of ion mobility, and which isdefined by the structure and operating parameters of the multiple-passdrift tube 14, and the set of ion gates, e.g., ion gates G1-G3 may thenbe controlled to pass or divert some or all of the ions travelingthrough the multiple-pass drift tube 14 back into the single-pass drifttube 12 where they are then directed to the ion outlet 20 of thesingle-pass drift tube. In one alternate embodiment, the set of iongates, e.g., ion gates G1-G3, may be controlled to pass or divert ionssome or all of the ions traveling through the single-pass drift tube 12into the multiple-pass drift tube 14, and the electric fields within themultiple-pass drift tube 14, along with the set of ion gates, e.g., iongates G1-G3, may then controlled in a known manner to confine thediverted ions within the multiple-pass drift tube 14 so that the ionsseparate in time according to a second function of ion mobility in whichonly the diverted ions within the ion mobility range of interest passone or more times through, i.e., about, the multiple-pass drift tube 14.The set of ion gates, e.g., ion gates G1-G3 may then be controlled topass or divert some or all of the ions traveling through themultiple-pass drift tube 14 back into the single-pass drift tube 12where they are then directed to the ion outlet 20 of the single-passdrift tube. In another alternate embodiment, the set of ion gates, e.g.,ion gates G1-G3, may be controlled to pass or divert some or all of theions traveling through the single-pass drift tube 12 into themultiple-pass drift tube 14, and the electric fields within themultiple-pass drift tube 14, along with the set of ion gates, e.g., iongates G1-G3, may then controlled in a known manner to confine thediverted ions within the multiple-pass drift tube 14 so that the ionsseparate in time according to a second function of ion mobility, whichmay or may not be the same as the first function of ion mobility, andwhich is defined by the structure and operating parameters of themultiple-pass drift tube 14. The ion gates, e.g., ion gates G1-G3, maythen be controlled to pass or divert some or all of the ions travelingthrough the multiple-pass drift tube 14 back into the single-pass drifttube 12, and one or more ion gates positioned within the drift tubesection D2 may be controlled to pass through the ion outlet 20 only ionswithin the ion mobility range of interest.

In some embodiments, one or more of the ion gates in the set of iongates, e.g., G1-G3, may be controlled to one or more intermediatepositions between the open and closed positions. In such embodiments,and according to another specific operating mode of the hybrid ionmobility spectrometer 10 illustrated in FIG. 1A, for example, the set ofion gates, e.g., ion gates G1-G3, may be controlled to direct some ofthe ions traveling through the single-pass drift 12 into themultiple-pass drift tube 14 while also allowing others of the ionstraveling through the single-pass drift tube 12 to travel completelythrough the single-pass drift tube 12, e.g., to and through the outlet20 thereof. In such an operating mode, ions supplied by the single orcommon ion source 18 to the inlet 16 of the single-pass drift tube 12thus travel in parallel through the single-pass drift tube 12 and thecombination of the single-pass drift tube 12 and the multiple-pass drifttube 14, with some of the ions traveling directly through thesingle-pass drift tube 12 to and through the ion outlet 20 and others ofthe ions traveling through the single-pass drift tube 12, to and throughthe multiple-pass drift tube 14, then back to and through any remainingsection(s) of the single-pass drift tube 12 and exiting the ion outlet20 of the single-pass drift tube 12.

In any case, further details relating to various structural embodimentsof the hybrid ion mobility spectrometer briefly described above and theforegoing operation thereof are described below and/or illustrated inthe attached drawings, although it will be understood that otherstructural embodiments and operational modes of the hybrid ion mobilityspectrometer illustrated and described herein will occur to thoseskilled in the art and that such other structural embodiments andoperational modes are contemplated by this disclosure.

Referring now specifically to FIG. 1A, an embodiment of the hybrid ionmobility spectrometer 10 briefly described above is shown. As describedabove, the hybrid ion mobility spectrometer 10 includes an ion source 18coupled to an ion inlet 16 defined at one end of a single-pass ionmobility spectrometer 12, and an ion outlet 20 is defined at an oppositeend of the single-pass ion mobility spectrometer 12. A multiple-pass ionmobility spectrometer 14 is coupled to the single-pass ion mobilityspectrometer 12 between the ion inlet 16 and the ion outlet 20 thereofsuch that ions may be selectively passed from the single-pass ionmobility spectrometer 12 to the multiple-pass ion mobility spectrometer14 and vice versa. For purposes of this disclosure, the term“single-pass ion mobility spectrometer” means an ion mobilityspectrometer, or portion thereof, through which ions pass a single time,and the term “multiple-pass ion mobility spectrometer” means an ionmobility spectrometer, or portion thereof, through which ions may passmultiple times. Neither such ion mobility spectrometer is limited to anyparticular shape or configuration, and the single-pass ion mobilityspectrometer 12 and/or the multiple-pass ion mobility spectrometer 14may be or include a linear, piecewise-linear and/or non-linear drifttube.

In the illustrated embodiment, the ion outlet 20 of the single-pass ionmobility spectrometer 12 is coupled to an ion detector 22 which isconfigured to detect, in a conventional manner, ions exiting the ionoutlet 20 of the single-pass ion mobility spectrometer 12. In alternateembodiments, one or more additional ion separation and/or ion analyzingapparatuses may be positioned between the ion outlet 20 of thesingle-pass ion mobility spectrometer 12 and the ion detector 22, and inany such alternate embodiment one or more ion detectors 22 may becoupled to or integral with any of the additional ion separation and/orion analyzing apparatuses, alternatively to or in addition to thesingle-pass ion mobility spectrometer 12.

The ion source 18 may be any conventional ion source, examples of whichinclude, but are not limited to, an electrospray ion source, amatrix-assisted laser desorption ion source (MALDI), or the like.Alternatively or additionally, the ion source 18 may include one or moreconventional apparatuses to collect all or a subset of the generatedions (i.e., within a defined range of ion mobilities and/or within adefined range of ion mass-to-charge ratios) and/or to structurallymodify, e.g., fragment and/or change the conformations of, some or allof the generated ions and/or to normalize or otherwise modify the chargestates of one or more of the generated ions. Alternatively oradditionally still, the ion source 18 may be or include one or moreknown apparatuses that separate ions and/or one or more isotopes thereofas a function of any molecular characteristic, e.g., ion mass-to-chargeratio, ion mobility, ion retention time, or the like.

In the embodiment illustrated in FIG. 1A, the single-pass ion mobilityspectrometer 12 is made up of three cascaded drift tube sections; afirst drift tube section D1 coupled to the ion source 18, a transitiondrift tube section DT coupled to the first drift tube section D1 and tothe drift tube of the multiple-pass ion mobility spectrometer 14, and asecond drift tube section D2 coupled to the transition drift tubesection DT and, in the illustrated embodiment, to the ion detector 22.In one embodiment, the first drift tube section D1 is illustratively alinear drift tube section and includes a cascaded arrangement of anynumber, N, of conventional linear drift tube sub-sections 30 _(N) (threesuch drift tube sub-sections 30 ₁, 30 ₂ and 30 ₃ shown) and any number,M, of conventional linear drift tube funnels 32 _(M) (two such drifttube funnels 32 ₁ and 32 ₂ shown), wherein a different drift tube funnel32 may be interposed between any number of cascaded drift tubesub-sections 30. The second drift tube section D2 is likewiseillustratively a linear drift tube section and may likewise include acascaded arrangement of any number, Q, of conventional drift tubesections 30 _(Q) (two such drift tube sub-sections 30 ₄ and 30 ₅ shown)and any number, R, of conventional drift tube funnels 32 _(R) (two suchdrift tube funnels 32 ₉ and 32 ₁₀ shown), wherein a different drift tubefunnel 32 may be interposed between any number of cascaded drift tubesub-sections 30. Alternatively, the second drift tube section D2 mayinclude only a single drift tube sub-section 30 or drift tube funnel 32which is coupled at one end to the transition drift tube section DT anddefines the ion outlet 20 of the single-pass ion mobility spectrometer12 at its opposite end. Alternatively still, the second drift tubesection D2 may be omitted altogether and the ion outlet of thetransition drift tube section DT may define the ion outlet 20 of thesingle-pass ion mobility spectrometer 12.

The drift tube sub-sections 30 and the drift tube funnels 32 illustratedin FIG. 1A are illustratively linear components in that each drift tubesub-section 30 and each drift tube funnel 32 defines a linear ion drifttube axis therethrough between an ion inlet and ion outlet thereof. Theresulting drift tube sections D1 and D2 shown in FIG. 1A thereforelikewise linear drift tube sections, it will be understood that eitheror both of the drift tube sections D1 and D2 may alternatively bepiecewise linear or non-linear, or include one or more piecewise linearor non-linear subsections.

In any case, the one or more drift tube funnels 32 are illustrativelycontrolled in a conventional manner to radially focus ions inwardlytoward a central ion drift axis defined through the drift tube funnel 32from an ion inlet to an ion outlet thereof. Additionally, one or more ofthe ion funnels 32 and/or one or more of the drift tube sub-sections 30may include one or more ion gates controllable in a conventional mannerto selectively pass ions therethrough or block ions from passingtherethrough. Alternatively or additionally, one or more of the ionfunnels 32 may include one or more regions that is/are controllable in aconventional manner to modify the structures of some or all of the ionspassing therethrough, e.g., via ion fragmentation and/or inducingconformational changes in the ions. Further details relating toillustrative embodiments of the drift tube sub-sections 30 and the drifttube funnels 32 shown in FIG. 1A and described above are described inU.S. Patent Pub. No. 2007/0114382 A1 and also in related U.S. Pat. No.8,618,475, the disclosures of which are incorporated herein byreference.

The transition drift tube section DT in the embodiment illustrated inFIG. 1A, is illustratively made up of a number, S, of curved drift tubesub-sections 34 _(S) (two such curved drift tube sub-sections 34 ₁ and34 ₂ shown, with the curved drift tube sub-section 34 ₁ defining an ioninlet to the transition drift tube section DT and coupled to the ionoutlet of the first drift tube section D1, and with the curved drifttube sub-section 34 ₂ defining an ion outlet of the transition drifttube section DT and coupled to the ion inlet of the second drift tubesection D2), a number, T, of the drift tube funnels 32 _(T) (three suchdrift tube funnels 32 ₃, 32 ₄ and 32 ₅ shown) and sub-sections of eachof two curved, Y-shaped drift tube sections 36 ₁ and 36 ₂. Themultiple-pass ion mobility spectrometer 14, in the embodimentillustrated in FIG. 1A, is illustratively provided in the form of aclosed-path drift tube made up of a number, U, of the curved drift tubesub-sections 34 _(U) (two such curved drift tube sub-sections 34 ₃ and34 ₄ shown), remaining sub-sections of the two curved, Y-shaped drifttube sections 36 ₁ and 36 ₂, and a number, V, of the drift tube funnels32 _(V) (four such drift tube funnels 32 ₅, 32 ₆, 32 ₇ and 32 ₈ shown).It will be understood, however, that the multiple-pass drift tube 14 mayalternatively not form a closed path but may nevertheless be configuredto pass ions multiple times therethrough.

In the embodiment illustrated in FIG. 1A, the sub-section or branch ofthe curved, Y-shaped drift tube section 36 ₁ that is coupled to thedrift tube funnel 32 ₃ serves the dual function as part of thesingle-pass ion mobility spectrometer 12 and also as an ion inlet to themultiple-pass ion mobility spectrometer 14, and the sub-section orbranch of the curved, Y-shaped drift tube section 36 ₂ that is coupledto the drift tube funnel 32 ₄ likewise serves the dual function as partof the single-pass ion mobility spectrometer 12 and also as an ionoutlet of the multiple-pass ion mobility spectrometer 14. The drift tubefunnel 32 ₅ is illustratively shared by the single-pass ion mobilityspectrometer 12 and the multiple-pass ion mobility spectrometer 14 andtherefore forms part of each. Further details relating to illustrativeembodiments of the curved drift tube sub-sections 34, the curvedY-shaped drift tube sections 36 and the closed-path configuration of themultiple-pass ion mobility spectrometer 14 shown in FIG. 1A anddescribed above are described in U.S. Pat. No. 8,362,420, the disclosureof which is incorporated herein by reference.

The hybrid ion mobility spectrometer 10 illustrated in FIG. 1A includesthree ion gates, G1-G3, each of which is controllable in a conventionalmanner to selectively allow ions to pass therethrough and to selectivelyblock ions from passing therethrough. In one embodiment, the ion gatesG1-G3 are each provided in the form of a mesh or grid, and a DCpotential applied thereto, or a DC differential applied between a meshor grid and an adjacent ring, is controlled such that at one DC level orDC differential value ions pass through the ion gate and at a differentDC level or DC differential value ions are blocked from passing throughthe ion gate. In alternate embodiments, the ion gate function of one ormore of the ion gates G1-G3 may be accomplished by selectively applyingand varying the frequency and/or amplitude of an RF voltage to anon-meshed or gridded ring, in a conventional manner, to selectivelyallow passage or block passage of ions therethrough. In someembodiments, one or more of the gates G1-G3 may be controlled withintermediate DC potentials and/or RF frequencies/amplitudes to passtherethrough only a portion of ions presented thereat, e.g., to allowpassage through one or more of the ion gates G1-G3 of only a percentageof ions that is less than 100% of the total number of ions travelingtoward the one or more ion gates G1-G3. In any case, the three ion gatesG1-G3 are controllable, as will be described in detail below, to confineions within the single-pass drift tube 12, to confine ions within themultiple-pass drift tube 14, to pass or divert at least some of the ionsin the single-pass drift tube 12 into the multiple-pass drift tube 14and/or to pass or divert at least some of the ions in the multiple-passdrift tube 14 back into the single-pass drift tube 12.

In the embodiment illustrated in FIG. 1A, a first one of the ion gates,G1, is illustratively positioned in the curved, Y-shaped drift tubesection 36 ₂ at an interface of the sub-section of the Y-shaped drifttube section 36 ₂ that is coupled to the drift tube funnel 32 ₅ and thesub-section or branch of the Y-shaped drift tube section 36 ₂ that iscoupled to the drift tube funnel 32 ₈. A second one of the ion gates,G2, is illustratively positioned in the curved, Y-shaped drift tubesection 36 ₂ at an interface of the sub-section of the Y-shaped drifttube section 36 ₂ that is coupled to the drift tube funnel 32 ₅ and thesub-section or branch of the Y-shaped drift tube section 36 ₂ that iscoupled to the drift tube funnel 32 ₄. A third one of the ion gate, G3,is illustratively positioned in the curved, Y-shaped drift tube section36 ₁ at an interface of the sub-section of the Y-shaped drift tubesection 36 ₁ that is coupled to the drift tube funnel 32 ₅ and thesub-section or branch of the Y-shaped drift tube section 36 ₁ that iscoupled to the drift tube funnel 32 ₃. It will be understood that thehybrid ion mobility spectrometer 10 may include more or fewer such iongates, and that any such alternative embodiment of the hybrid ionmobility spectrometer is contemplated by this disclosure.

In one alternate embodiment of the hybrid ion mobility spectrometer 10,one or more of the drift tube sub-sections 30, 34, 36 and/or one or moreof the drift tube funnels 32 may be provided in the form of a two-partsub-section or funnel defining a first drift tube region having an ioninlet defining the ion inlet of the sub-section or funnel and an ionoutlet coupled to an ion inlet of an ion elimination region having anion outlet defining the ion outlet of the sub-section or funnel. Furtherdetails relating to the structure and various operational modes of suchalternately configured drift tube sub-sections and/or funnels aredescribed in co-pending U.S. Patent Application Pub. No. 2013/0292562,the disclosure of which is incorporated herein by reference.

In another alternate embodiment of the hybrid ion mobility spectrometer10, one or more of the drift tube funnels 32 and/or one or more of thedrift tube sub-sections 30, 34, 36 may be provided in the form of aconventional drift tube sub-section 30 to which RF voltages may beapplied to radially focus ions inwardly toward the ion drift pathdefined therethrough. One illustrative embodiment of such a drift tubesub-section 50 is shown in FIG. 2, and includes a series ofidentically-dimensioned, electrically insulating rings 56 eachseparating adjacent ones of a series of identically-dimensioned,electrically conductive rings 58, with all such rings 56, 58 stacked andclamped together between an ion inlet 52 and an ion outlet 54 of thedrift tube sub-section 50. Illustratively, the last several, e.g., two,electrically insulating rings may be (but need not be) provided in theform of reduced-thickness rings 60 (e.g., approximately ½ of thethickness of the rings 56), the purpose which will be described below.

In the illustrated embodiment, an RF voltage source 70 produces two RFvoltages, φ₁ and φ₂ each 180 degrees out of phase with respect to theother, with φ₁ applied via a separate capacitor, C1, to all odd (oreven) numbered rings 58 and φ₂ applied via a separate capacitor, C1, toall even (or odd) numbered rings 58 such that φ₁ and φ₂ are appliedalternately to the series of rings 58 in the stack. A DC potential isapplied via series-connected resistors, R, to the rings 58 to create asubstantially uniform electric drift field in the drift tube sub-section50, and ions drift through the drift tube sub-section 50 under theinfluence of the electric drift field. The frequencies and/or amplitudesof the RF voltages φ₁ and φ₂ are illustratively selected in aconventional manner to radially focus ions drifting through the drifttube sub-section 50 toward an ion drift axis defined centrally throughthe drift tube sub-section 50. In embodiments in which thereduced-width, electrically insulating rings 60 are included, another RFvoltage source 72 may be provided to produce an RF voltage φ₃ that isapplied through a different capacitor, C2, to each of the electricallyconductive rings 58 contacting one of the rings 60. The frequency and/oramplitude of φ₃ is controlled in a conventional manner to selectivelyallow passage of ions through the electrically conductive rings 58connected to φ₃ or block passage of ions therethrough to thereby providean ion gating function.

The drift tube sub-sections 50 with the radial ion focusing featuredescribed above may be used in place of one or more of the drift tubefunnels 32 and/or in place of one or more of the drift tube sub-sections30, 34, 36 illustrated in FIG. 1A. Alternatively or additionally, thedrift tube sub-sections 50 with or without the radial ion focusingfeature but with the ion gating feature described above may be used inplace of one or more of the ion gates G1-G3 illustrated in FIG. 1A. Inany of the embodiments illustrated in the attached figures and describedherein, either or both of the single-pass drift tube and themultiple-pass drift tube may be operated in a conventional travelingwave operating mode, i.e., one in which one or more oscillating, i.e.,AC, electric fields are established within the various drift tubesections to cause the ions to separate as they drift through therespective drift tube.

Referring again to FIG. 1A, a number of voltage sources 40 areelectrically connected to various parts of the hybrid ion mobilityspectrometer 10, and the number of voltage sources 40 are selected andcontrolled to apply appropriate DC and/or AC voltages to the variousparts and components of the hybrid ion mobility spectrometer 10 foroperation thereof. For example, one or more of the voltage sources 40is/are electrically connected to the ion source 18 to control the ionsource 18 in a conventional manner to generate, collect and/or processions as described above. One or more others of the voltage sources 40is/are electrically connected to each drift tube sub-section 30, 34, 36and each drift tube funnel 32 to establish an electric drift fieldtherein through which ions traverse the single-pass drift tube 12 andthe multiple-pass drift tube 14. One or more others of the voltagesources 40 is/are electrically connected to the drift tube funnels 32 toradially focus ions inwardly toward the drift tube axis definedtherethrough, and/or to control operation of one or more ion gatescontained therein to pass or block ions, and/or to control one or moreion activation regions included in one or more of the funnels 32 tomodify the structure of ions passing therethrough, e.g., via ionfragmentation and/or by inducing conformational changes in ions withoutfragmenting them. One or more others of the voltage sources 40 is/areelectrically connected to each of the ion gates G1-G3 and selectivelycontrolled to pass or block ions as described above and as will bedescribed in greater detail below with respect to the processillustrated in FIG. 3. In any case, the one or more voltage sources 40are conventional and may be individually programmed for operation orcontrolled by a processor 42 (e.g., amplitude, frequency, timing ofactivation and/or deactivation, etc.) as shown by dashed-linerepresentation. The processor 42 is, in any event, electricallyconnected to the ion detector, and the processor 42 includes a memoryhaving instructions stored therein that are executable by the processor42 to process ion detection signals produced by the ion detector 22 andproduce corresponding ion mobility spectral information, e.g., as afunction of ion drift time through the single-pass drift tube 12 and/orthe multiple-pass drift tube 14.

A gas source 44, e.g., single buffer gas, combination of gases to form abuffer gas, one or a combination of other gases, etc., is fluidlycoupled to the hybrid ion mobility spectrometer 10 via a fluid conduit46. In embodiments of the hybrid ion mobility spectrometer 10constructed from open-ended sub-sections 30, 34, 36 and with or withoutopen-ended drift tube funnels 32, the resulting spectrometer 10 is acontinuous cavity spectrometer, and the single gas source 44 may thus beused to fill the entire spectrometer 10, including the single-pass drifttube 12 and the multiple-pass drift tube 14. In alternative embodiments,two or more gas sources may be used, and the hybrid ion mobilityspectrometer 10 may be partitioned in a conventional manner to confinethe two or more gases to corresponding portions of the spectrometer 10.The gas source 44 may be manually controlled, programmable for automaticcontrol and/or controlled by the processor 42 as shown by dashed-linerepresentation in FIG. 1A.

Referring now to FIG. 1B, an alternate embodiment of a hybrid ionmobility spectrometer 10′ is shown. The hybrid ion mobility spectrometer10′ is identical in many respects to the hybrid ion mobilityspectrometer 10 illustrated in FIG. 1A and described above. Likefeatures are identified by like reference numbers, and a detaileddescription of common features between the two spectrometers 10 and 10′will not be repeated here for brevity. It will be further understoodthat the various embodiments of the various components and aspects tothe hybrid ion mobility spectrometer 10 described above apply equally tothe hybrid ion mobility spectrometer 10′.

The hybrid ion mobility spectrometer 10′ illustrated in FIG. 1B differsfrom the hybrid ion mobility spectrometer 10 illustrated in FIG. 1Aprimarily in the construction of the single-pass drift tube 12′ and inthe number and location of the various ion gates that are controlled toachieve operation of the spectrometer 10 as described above. In theembodiment illustrated in FIG. 1B, for example, the drift tube funnel 32₃ is coupled at its ion inlet to one ion outlet branch of a Y-shapeddrift tube sub-section 38 ₁ having another ion outlet branch coupled toan ion inlet of another drift tube funnel 32 ₁₁, wherein both such ionoutlet branches are coupled to a common ion inlet branch having an ioninlet coupled to an ion outlet of the drift tube funnel 32 ₂. The drifttube funnel 32 ₄ is similarly coupled at its ion outlet to one ion inletbranch of another Y-shaped drift tube sub-section 38 ₂ having anotherion inlet branch coupled to an ion outlet of the drift tube funnel 32₁₁, wherein both such ion outlet branches are coupled to a common ionoutlet branch having an ion outlet coupled to an ion outlet of the drifttube funnel 32 ₉. In this embodiment, the single-pass drift tube 12′ isa linear drift tube made up of the linear drift tube segments D1 and D2joined by a linear drift tube segment D3 made up of the linear branchesof the Y-shaped drift tube sub-sections 38 ₁, 38 ₂ and the drift tubefunnel 32 ₁₁.

The embodiment illustrated in FIG. 1B includes four ion gates G1-G4which are controllable, as will be described in detail below, to confineions within the single-pass drift tube 12′, to confine ions within themultiple-pass drift tube 14, to pass or divert at least some of the ionsin the single-pass drift tube 12′ into the multiple-pass drift tube 14and/or to pass or divert at least some of the ions in the multiple-passdrift tube 14 back into the single-pass drift tube 12′. A first one ofthe ion gates, G1, is illustratively positioned in the Y-shaped drifttube section 38 ₁ at an interface of the curved branch of the Y-shapeddrift tube section 38 ₁ that is coupled to the drift tube funnel 32 ₁and the branch of the Y-shaped drift tube section 38 ₁ that is coupledto the drift tube funnel 32 ₂. A second one of the ion gates, G2, isillustratively positioned in the Y-shaped drift tube section 38 ₁ at aninterface of the linear branch of the Y-shaped drift tube section 38 ₁that is coupled to the drift tube funnel 32 ₁₁ and the branch of theY-shaped drift tube section 38 ₁ that is coupled to the drift tubefunnel 32 ₂. A third one of the ion gates, G3, is illustrativelypositioned in the curved, Y-shaped drift tube section 36 ₂ at aninterface of the sub-section of the Y-shaped drift tube section 36 ₂that is coupled to the drift tube funnel 32 ₅ and the sub-section orbranch of the Y-shaped drift tube section 36 ₂ that is coupled to thedrift tube funnel 32 ₈. A fourth one of the ion gates, G4, isillustratively positioned in the curved, Y-shaped drift tube section 36₂ at an interface of the sub-section of the Y-shaped drift tube section36 ₂ that is coupled to the drift tube funnel 32 ₅ and the sub-sectionor branch of the Y-shaped drift tube section 36 ₂ that is coupled to thedrift tube funnel 32 ₄. It will be understood that the hybrid ionmobility spectrometer 10′ may include more or fewer such ion gates, andthat any such alternative embodiment of the hybrid ion mobilityspectrometer is contemplated by this disclosure.

Referring now to FIG. 1C, another alternate embodiment of a hybrid ionmobility spectrometer 10″ is shown. The hybrid ion mobility spectrometer10″ is also identical in many respects to the hybrid ion mobilityspectrometer 10 illustrated in FIG. 1A and described above. Likefeatures are identified by like reference numbers, and a detaileddescription of common features between the two spectrometers 10 and 10″will not be repeated here for brevity. It will be further understoodthat the various embodiments of the various components and aspects tothe hybrid ion mobility spectrometer 10 described above apply equally tothe hybrid ion mobility spectrometer 10″.

The hybrid ion mobility spectrometer 10″ illustrated in FIG. 1C differsfrom the hybrid ion mobility spectrometer 10 illustrated in FIG. 1Aprimarily in the construction of each of the single-pass drift tube 12″and the multiple-pass drift tube 14′, and also in the location of thevarious ion gates that are controlled to achieve operation of thespectrometer 10 as described above. In the embodiment illustrated inFIG. 1C, for example, the drift tube funnel 32 ₂ is coupled at its ionoutlet to an ion inlet of a drift tube sub-section 30 ₅, and an ionoutlet of the drift tube sub-section 30 ₅ is coupled to an ion inlet ofthe drift tube funnel 32 ₃ (corresponding to the drift tube funnel 32 ₉in FIG. 1A). In this embodiment, the single-pass drift tube 12″ is thusa linear drift tube made up of the linear drift tube segments D1 and D2joined by a linear drift tube segment DT made up of the drift tubesub-section 30 ₅. The multiple-pass drift tube 14′ is, in the embodimentillustrated in FIG. 1C, a closed-path drift tube made up of four curveddrift tube sub-sections 34 ₁-34 ₄ each coupled between a different twoof four drift tube funnels 32 ₅-32 ₈. A drift tube section 30 ₈ has anion inlet coupled to the drift tube sub-section 30 ₅ of the single-passdrift tube 12″ and an ion outlet coupled to an ion inlet of a drift tubesection 35. An ion outlet of the drift tube section 35 is coupled to thedrift tube sub-section 34 ₂ of the multiple pass drift tube 14′. In someembodiments, such as that illustrated in FIG. 1C, the drift tube section35 may include an inlet/outlet, i.e. bi-directional, funnel which may becontrolled in a conventional manner, e.g., via one or more voltagesources, to direct and focus ions moving from the single-pass drift tube12″ into the multiple-pass drift tube 14′ via the drift tube sub-section30 ₈, and which may also be controlled in a conventional manner, e.g.,via one or more voltage sources, to direct and focus ions moving fromthe multiple-drift tube 14′ into the single-pass drift tube 12″ via thedrift tube sub-section 30 ₈. In other embodiments, the bi-directionalfunnel may be replaced with another funnel structure or other mechanism(e.g., structure and/or energy source(s)), or omitted altogether. In anycase, the drift tube sections 30 ₈, 35 form a T-connection between thesingle pass drift tube 12″ and the multiple-pass drift tube 14′.

The embodiment illustrated in FIG. 1C includes three ion gates G1-G3which are controllable, as will be described in detail below, to confineions within the single-pass drift tube 12″, to confine ions within themultiple-pass drift tube 14′, to pass or divert at least some of theions in the single-pass drift tube 12″ into the multiple-pass drift tube14′ and/or to pass or divert at least some of the ions in themultiple-pass drift tube 14′ back into the single-pass drift tube 12″. Afirst one of the ion gates, G1, is illustratively positioned in thedrift tube sub-section 30 ₅ at or just beyond the ion inlet of the drifttube section 30 ₈. A second one of the ion gates, G2, is illustrativelypositioned in the drift tube section 30 ₈ at or just beyond the ioninlet thereof. A third one of the ion gates, G3, is illustrativelypositioned in the drift tube section 35 at or near the ion outletthereof. It will be understood that the hybrid ion mobility spectrometer10″ may include more or fewer such ion gates, and that any suchalternative embodiment of the hybrid ion mobility spectrometer iscontemplated by this disclosure.

Referring now to FIGS. 1D-1F, yet another alternate embodiment of ahybrid ion mobility spectrometer 10′″ is shown. The hybrid ion mobilityspectrometer 10′″ is also identical in many respects to the hybrid ionmobility spectrometers 10 and 10″ illustrated in FIGS. 1A and 1Crespectively and described above. Like features are identified by likereference numbers, and a detailed description of common features betweenthe spectrometers 10, 10″ and 10′″ will not be repeated here forbrevity. It will be further understood that the various embodiments ofthe various components and aspects to the hybrid ion mobilityspectrometer 10 and 10″ described above apply equally to the hybrid ionmobility spectrometer 10′″.

In one aspect, the hybrid ion mobility spectrometer 10′″ illustrated inFIGS. 1D-1F differs from the hybrid ion mobility spectrometer 10 and 10″illustrated in FIGS. 1A and 1C respectively in that an ion travel axis70 of the multiple-pass drift tube 14″, i.e., an axis defined, orparallel with an axis defined, centrally through the multiple-pass drifttube 14″ and along which ions travel through the multiple-pass drifttube 14″, lies in a plane that is different from the plane in which anion travel axis 72 of the single-pass drift tube 12′″, i.e., an axisdefined, or parallel with an axis defined, centrally through thesingle-pass drift tube 12′″ and along which ions travel through thesingle-pass drift tube 12′″, lies. In the illustrated embodiment, theplanes in which the ion travel axes 70 and 72 lie are orthogonal,although it will be understood that this disclosure contemplatesembodiments in which the two different planes in which the ion travelaxes 70 and 72 lie are not orthogonal.

In another aspect, the hybrid ion mobility spectrometer 10′″ illustratedin FIGS. 1D-1F differs from the hybrid ion mobility spectrometer 10 and10″ illustrated in FIGS. 1A and 1C respectively in that, in contrast toa drift tube transition section, DT, the hybrid ion mobilityspectrometer 10′″ defines a transition region 80 (TR) as an interfacebetween the single-pass drift tube 12′″ and the multiple-pass drift tube14″. Referring specifically to FIG. 1F, an example embodiment of thetransition region 80 is illustrated. In this embodiment, the transitionregion 80 includes a first plate 82 defining an ion passage, e.g.,opening, 90 therethrough, which represents an ion inlet to thetransition region 80 positioned adjacent to the ion outlet of the drifttube funnel 32 ₂ (e.g., see FIG. 1E). Another plate 84 is positionedopposite to the plate 80 and defines another ion passage, e.g., opening,92 therethrough (both shown by dashed-line representation in FIG. 1F),which represents an ion outlet of the transition region 80 positionedadjacent to the ion inlet of the drift tube funnel 32 ₃. A third plate86 is positioned between the plates 82 and 84 along one side thereof,and a fourth plate 88 is positioned between the plates 82 and 84 alonganother side thereof. The third and fourth plates 86, 88 each define anion passage, e.g., opening, therethrough which represent an ioninlet/outlet to/of the transition region 80 with the opening definedthrough the plate 86 positioned adjacent to the ion inlet/outlet of thedrift tube sub-section 34 ₁ and the opening defined through the plate 88positioned adjacent to the ion inlet/outlet of the drift tube section 34₂. One or more of the plates 82, 84, 86, 88 may illustratively beoperated as an ion gate, such that the illustrated embodiment mayinclude one or more of G1-G4.

As described briefly hereinabove, the ion gates G1-G3 of the hybrid ionmobility spectrometers 10 and 10″ and the ion gates G1-G4 of the hybridion mobility spectrometer 10′ and 10′″ are controllable to confine ionswithin the single-pass drift tube 12, 12′, 12″, 12′″, to confine ionswithin the multiple-pass drift tube 14, 14′, 14″ to pass or divert atleast some of the ions in the single-pass drift tube 12, 12′, 12″, 12′″into the multiple-pass drift tube 14, 14′, 14″ and/or to pass or divertat least some of the ions in the multiple-pass drift tube 14, 14′, 14″back into the single-pass drift tube 12, 12′, 12″, 12″. Referring now toFIGS. 3A and 3B, a flowchart is shown illustrating a process 100 forcontrolling the hybrid ion mobility spectrometer 10, 10′, 10″, 10′″according to a number of different operational modes of the hybrid ionmobility spectrometer 10, 10′, 10″, 10′″ in which the set of ion gates,e.g., ion gates G1-G3 for the spectrometers 10, 10″ and ion gates G1-G4for the spectrometer 10′, 10′″, are controlled as described above. Inone embodiment, some or all of the process 100 may be controlled by theprocessor 42 in accordance with instructions stored in a memory of theprocessor 42. Alternatively or additionally, some or all of the process100 may be controlled by programming one or more of the one or morevoltage sources 40 in embodiments in which one or more of the voltagesources 40 are programmable. Some of the process 100 may bealternatively or additionally carried out manually.

In any case, the process 100 begins at step 102 where the ion source 18is controlled in a conventional manner to generate ions, e.g., inembodiments in which the ion source 18 is or includes an ion generationstructure for generating ions from a sample, or to otherwise supplyions, e.g., in embodiments in which the ion source 18 is another ionseparation instrument and/or other ion processing instrument that doesnot itself generate ions but rather operates on ions generatedelsewhere. Thereafter at step 104, at least some of the generated orotherwise supplied ions are introduced into the ion inlet 16 of thesingle-pass drift tube 12, 12′, 12″, 12′″, e.g., by controlling aconventional ion gate positioned at the ion inlet 16 to pass ionstherethrough and into the single-pass drift tube 12, 12′, 12″, 12′″, bydrawing generated ions into the single-pass drift tube 12, 12′, 12″,12′″ using a static or dynamic electric field, or the like. At step 106,an electric drift field is established within the single-pass drift tube12, 12′, 12″, 12′″, which may occur before or after step 104.

In any case, the process 100 advances to step 108 where the ion gates,e.g., G1-G3 in the case of the hybrid ion mobility spectrometer 10, 10″and G1-G4 in the case of the hybrid ion mobility spectrometer 10′, 10′″,are controlled to direct ions in the single-pass drift tube 12, 12′,12″, 12′″ therethrough and through the ion outlet 20, i.e., to confineions within the single-pass drift tube 12, 12′, 12″, 12′″ such that theions drift only through the single-pass drift tube 12, 12′, 12″, 12′″from the ion inlet 16 to the ion outlet 20 thereof and not through themultiple-pass drift tube 14, 14′, 14″. In the single-pass drift tube 12illustrated in FIG. 1A, step 108 may be carried out by controlling G1 tothe closed or ion-blocking position and controlling G2 and G3 to theopen or ion-passing position, such that ions entering the ion inlet 16pass sequentially through D1, DT and D2 of the single-pass drift tube12. In the single-pass drift tube 12′ illustrated in FIG. 1B, step 108may be carried out by controlling G1 to the closed or ion-blockingposition and controlling G2 to the open or ion-passing position, suchthat ions entering the ion inlet 16 pass sequentially through D1, D3 andD2 of the single-pass drift tube 12′. In the single-pass drift tube 12″illustrated in FIG. 1C, step 108 may be carried out by controlling G1 tothe open or ion-passing position and controlling G2 to the closed orion-blocking position, such that ions entering the ion inlet 16 passsequentially through D1, DT and D2 of the single-pass drift tube 12″. Inthe single-pass drift tube 12′″ illustrated in FIGS. 1D-1F, step 108 maybe carried out by controlling G1, e.g., the opening 90 through the plate82, to the open or ion-passing position and controlling G2, e.g., theopening 92 through the plate 84, to the open or ion-passing position,and likewise controlling the gates G3, G4, e.g., the openings throughthe plates 86, 88 respectively to the closed or ion blocking positions,such that ions entering the ion inlet 16 pass sequentially through D1,TR and D2 of the single-pass drift tube 12′″. In each case, ionsgenerated at or otherwise supplied by the ion source 18 travel, i.e.,drift, through only the single-pass drift tube 12, 12′, 12″, 12′″ underthe influence of the electric field established therein where theyseparate in time as a first function of ion mobility defined by thevarious structural dimensions and operating parameters of thesingle-pass drift tube 12, 12′, 12″, 12′″.

Following step 108, the process 100 advances to step 110 where an ionmobility range of interest is determined based on at least some of theions exiting the single-pass drift tube 12, 12′, 12″, 12′″. As describedabove, it may be discovered upon analysis of ion spectral informationresulting from the detection of ions exiting the ion outlet 20 of thesingle-pass drift tube 12, 12′, 12′, 12″″ pursuant to step 108 that asubset, e.g., two or more, of ion intensity peaks in a particular rangeof ion mobilities (or ion drift times) are crowded together and cannotbe satisfactorily resolved over the length of the single-pass drift tube12, 12′, 12″, 12′″. Such a range of ion mobilities may then be the ionmobility range of interest. In other cases, the ion mobility range ofinterest may be determined based on one or more alternate or additionalcriteria. In some cases, the ion mobility range of interest may be thesame as that produced by the single-pass drift tube 12, 12′, 12″, 12′″,and in other cases the ion mobility range of interest may be differentas just described. Likewise, whereas the single-pass drift tube 12, 12′,12″, 12′″ is generally operable to separate ions according to a firstfunction of ion mobility and the multiple-pass drift tube 14, 14′, 14″is generally operable to separate ions according to a second function ofion mobility, the first and second functions of ion mobility may be thesame in some embodiments and different in others.

In one embodiment, the process 100 includes a step 112 as shown indashed-line representation, and in this embodiment the process 100advances from step 110 to step 114 wherein the single-pass drift tube12, 12′, 12″, 12′″ is cleared of ions, e.g., by stopping the generationof ions by the ion source 18 and allowing the tube 12, 12′, 12″, 12′″ toclear. Thereafter at step 116, the ion source 18 is controlled to begingenerating ions again, and thereafter at step 118 at least some of thegenerated ions are introduced into the single-pass drift tube 12, 12′,12″, 12′″ as described above with respect to step 104. In alternateembodiments, the process 100 does not include step 112 and in some suchembodiments the ion source 18 may be controlled to continually,periodically or intermittently generate ions while in other embodimentsthe ion source 18 may be started and then stopped, but ions need not becleared from the single-pass drift tube 12, 12′, 12″, 12′″ beforecontinuing to step 120.

At step 120, the set of ion gates, e.g., G1-G3 in the case of the hybridion mobility spectrometer 10, 10′″ and G1-G4 in the case of the hybridion mobility spectrometer 10′, 10′″, is controlled to divert or passsome or all of the ions in or entering the single-pass drift tube 12,12′, 12″, 12′″ into the multiple-pass drift tube 14, 14′, 14″, and atstep 122 an electric field is established within the multiple-pass drifttube 14, 14′, 14″ to cause ions to drift through the multiple-pass drifttube 14, 14′, 14″. In the single-pass drift tube 12 illustrated in FIG.1A, step 120 may be carried out by controlling G1 and G3 to their openor ion-passing positions and controlling G2 to the closed orion-blocking position, such that ions entering the ion inlet 16 passsequentially through D1, through part of DT and into the multiple-passdrift tube 14. In the single-pass drift tube 12′ illustrated in FIG. 1B,step 120 may be carried out by controlling G1 and G3 to their open orion-passing positions, and controlling G2 and G4 to their closed orion-blocking positions, such that ions entering the ion inlet 16 passfrom D1 directly into the multiple-pass drift tube 14. In thesingle-pass drift tube 12″ illustrated in FIG. 1C, step 120 may becarried out by controlling G1 to the closed or ion-blocking position,and controlling G2 and G3 to their open or ion-passing positions withthe electric drift field in the drift tube sections 30 ₈ and 35controlled to pass ions moving through D1 into the multiple-pass drifttube 14′. In the single-pass drift tube 12′″ illustrated in FIGS. 1D-1F,step 120 may be carried out by controlling G1, e.g., the opening 90through the plate 82, to the open or ion-passing position, controllingG2, e.g., the opening 92 through the plate 84, to the closed orion-blocking position, and controlling the gates G3 and/or G4, e.g., theopenings through the plates 86, 88 respectively to the open orion-passing positions, such that ions entering the ion inlet 16 passfrom D1 through TR and directly into the multiple-pass drift tube 14″.Ions generated at the ion source 18 thus travel, i.e., drift, throughthe single-pass drift tube 12, 12′, 12″, 12′″ under the influence of theelectric field established therein where they separate in time as afirst function of ion mobility defined by the various structuraldimensions and operating parameters of the single-pass drift tube 12,12′, 12″, 12′″, and after passage of some or all of such ions into themultiple-pass drift tube 14, 14′, 14″ the ions travel, i.e., drift,through the multiple-pass drift tube 14, 14′, 14″ under the influence ofthe electric field established therein where they separate in time as asecond function of ion mobility defined by the various structuraldimensions and operating parameters of the multiple-pass drift tube 14,14′, 14″. The first and second functions of ion mobility may be the samein some embodiments and different in others.

At step 124, the set of ion gates, e.g., G1-G3 in the case of the hybridion mobility spectrometer 10, 10″ and G1-G4 in the case of the hybridion mobility spectrometer 10′, 10′″, is controlled to cause ions withinthe multiple-pass drift tube 14, 14, 14″ to travel one or multiple timesthrough or about the multiple-pass drift tube 14, 14′, 14″. The numberof times the ions travel through or about the multiple-pass drift tube14, 14′, 14″ will typically be dictated by the total length of themultiple-pass drift tube 14, 14′, 14″ needed to adequately resolve theion peaks of interest, or by other additional or alternate criteria. Inthe single-pass drift tube 12 illustrated in FIG. 1A, step 124 may becarried out by maintaining G1 in its open or ion-passing position and G2in its closed or ion-blocking position, and controlling G3 to its closedposition such that the multiple-pass drift tube 14 is completely closedto the single-pass drift tube 12. In the single-pass drift tube 12′illustrated in FIG. 1B, step 124 may be carried out by maintaining G3and in its open or ion-passing position and G4 in its closed orion-blocking position, and controlling G1 to its closed or ion-blockingposition such that the multiple-pass drift tube 14 is completely closedto the single-pass drift tube 12′. In the single-pass drift tube 12″illustrated in FIG. 1C, step 124 may be carried out by controlling G2and/or G3 to closed or ion-blocking position, such that themultiple-pass drift tube 14′ is completely closed to the single-passdrift tube 12″. In the single-pass drift tube 12′″ illustrated in FIGS.1D-1F, step 124 may be carried out by controlling G1, G2, e.g., theopenings through the plates 82, 84 respectively, to their closed orion-blocking positions, and controlling G3, G4, e.g., the openingsthrough the plates 86, 88 respectively, to their open or ion-passingpositions, such that the multiple-pass drift tube 14″ is completelyclosed to the single-pass drift tube 12′″. The ions then travel, i.e.,drift, through the multiple-pass drift tube 14, 14′, 14″ under theinfluence of the electric field established therein where they separatein time as a second function of ion mobility defined by the variousstructural dimensions and operating parameters of the multiple-passdrift tube 14, 14′, 14″.

In one embodiment, step 126 is included, and at step 126 the electricdrift field established within the multiple-pass drift tube 14, 14′, 14″is controlled to cause only ions within the ion mobility range ofinterest to travel through the multiple-pass drift tube 14, 14′, 14″.For example, the open/closed timing of the various ion gates (G1-G3 orG1-G4) may be controlled at step 120 to pass ions of all mobilities fromthe single-pass drift tube 12, 12′, 12″, 12′″ into the multiple-passdrift tube 14, 14′, 14″, and in such embodiments, electric fields withinthe sub-sections 34 and funnels 32 of the multiple-pass drift tube 14,14′, 14″ are sequentially switched on and off in a conventional mannerat a rate that allows only ions within the ion mobility range ofinterest to traverse the multiple-pass drift tube 14, 14′, 14″. In somealternate embodiments, the open/closed timing of the ion gates G1-G3 (orG1-G4) may be controlled at step 120 such that only ions within the ionmobility range of interest are passed from the single-pass drift tube12, 12′, 12″, 12′″ into the multiple-pass drift tube 14, 14′, 14″, andin such embodiments step 126 may be carried out simply by controllingthe application of the electric fields within the sub-sections 34 andfunnels 32 of the multiple-pass drift tube 14, 14′, 14″ to pass ions ofall ion mobilities or by sequentially switching such electric fields onand off at a rate that allows only ions within the ion mobility range ofinterest to continue to traverse the multiple-pass drift tube 14, 14′,14″.

After the ions have traveled the multiple times through themultiple-pass drift tube 14, 14′, 14″ the set of ion gates, e.g., G1-G3in the case of the hybrid ion mobility spectrometer 10, 10″ and G1-G4 inthe case of the hybrid ion mobility spectrometer 10′, 10′″ is controlledat step 128 to pass at least some of the ions from the multiple-passdrift tube 14, 14′, 14″ back into the single-pass drift tube 12, 12′,12″, 12′″. In the single-pass drift tube 12 illustrated in FIG. 1A, step128 may be carried out by controlling G1 to the closed or ion-blockingposition and controlling G2 to the open or ion-passing position, suchthat ions traveling through the multiple-pass drift tube 14 pass backinto the single-pass drift tube 12, i.e., sequentially via the Y-shapeddrift tube segment 36 ₂, the drift tube funnel 32 ₄ and the curved drifttube sub-section 34 ₂. In the single-pass drift tube 12′ illustrated inFIG. 1B, step 128 may be carried out by controlling G3 to the closed orion-blocking position and controlling G4 to the open or ion-passingposition, such that ions traveling through the multiple-pass drift tube14 pass back into the single-pass drift tube 12′, i.e., sequentially viathe Y-shaped drift tube segment 36 ₂, the drift tube funnel 32 ₄ and thecurved branch of the Y-shaped drift tube sub-section 38 ₂. In thesingle-pass drift tube 12″ illustrated in FIG. 1C, step 128 may becarried out by controlling G1, G2 and G3 to their open or ion-passingpositions with the electric fields in the drift tube sections 30 ₈ and35 set to direct ions from the drift tube 34 ₂ to the drift tubesub-section 30 ₅. In the single-pass drift tube 12′″ illustrated inFIGS. 1D-1F, step 128 may be carried out by controlling G1 and either G3or G4, e.g., the openings through the plates 82 and 86 or 88respectively, to their closed or ion-blocking positions, and controllingG2 and the other of G3 or G4, e.g., the openings through the plates 84and 88 or 86 respectively, to their open or ion-passing positions, suchthat ions traveling through the multiple-pass drift tube 14″ pass backinto the single-pass drift tube 12′″ via the transition region 80.

In one embodiment, ions re-entering the single-pass drift tube 12, 12′,12″, 12′″ travel, i.e., drift, through the remainder of the single-passdrift tube 12, 12′, 12″ toward and through the ion outlet 20 under theinfluence of the electric field established therein where they separatein time in D2 according to the first function of ion mobility. In somealternate embodiments, the open/closed timing of the ion gates G1-G3 (orG1-G4) may be controlled at step 120 such that ions within all ionmobility ranges are passed from the single-pass drift tube 12, 12′, 12″,12′″ into the multiple-pass drift tube 14, 14′, 14″, step 126 may bereplaced by a step in which the open/closed timing of the ions gatesG1-G3 (or G1-G4) are likewise controlled such that ions within all ionmobility ranges travel through the multiple-pass drift tube 14, 14′,14″, step 128 may be modified to control the open/closed timing of theion gates G1-G3 (or G1-G4) such that ions within all ion mobility rangesare passed from the multiple-pass drift tube 14, 14′, 14″ back into thesingle-pass drift tube 12, 12′, 12″, 12′″, and one or more additionalion gates within D2, e.g., an ion gate positioned at the ion outlet 20,may be controlled by selectively controlling the open/closed positionsof the one or more additional ion gates, e.g., relative to anopening/closing of one or more upstream ion gates, such that only ionswithin the ion mobility range of interest exit the ion outlet 20 of thesingle-pass drift tube 12, 12′, 12″, 12′″.

Ions traveling through the ion outlet 20 are detected at step 130 by theion detector, and thereafter at step 132 the detected ions are processedby the processor 42 to produce corresponding ion spectral information,e.g., as a function of ion drift time.

In an alternate embodiment, the process 100 illustratively includes astep 134 between steps 120 and 122 such that the single-pass drift tube12, 12′, 12″, 12′″ and the multiple-pass drift tube 14, 14′, 14″ operatein parallel as described hereinabove. In one embodiment, step 134 mayinclude steps 102-110 as illustrated in FIG. 3A. In other embodiments,step 134 may include only steps 102-108, and in still other embodimentsin which ions are generated or otherwise supplied continually,intermittently or periodically step 134 may include only steps 104-108or 104-110. In other embodiments still, step 134 may include more, fewerand/or other steps than those just described. In any such embodiments,one or more of the ion gates in the set of ion gates, e.g., G1-G3, maybe controlled to one or more intermediate positions between the open andclosed positions to direct some of the ions traveling through thesingle-pass drift 12 into the multiple-pass drift tube 14 while alsoallowing others of the ions traveling through the single-pass drift tube12 to travel completely through the single-pass drift tube 12, e.g., toand through the outlet 20 thereof. In such a parallel operating mode,ions supplied by the single or common ion source 18 to the inlet 16 ofthe single-pass drift tube 12 thus travel in parallel through thesingle-pass drift tube 12 and also through the combination of thesingle-pass drift tube 12 and the multiple-pass drift tube 14, with someof the ions traveling directly through the single-pass drift tube 12 toand through the ion outlet 20 and others of the ions traveling throughthe single-pass drift tube 12, to and through the multiple-pass drifttube 14, then back to and through any remaining section(s) of thesingle-pass drift tube 12 and exiting the ion outlet 20 of thesingle-pass drift tube 12.

While the invention has been illustrated and described in detail in theforegoing drawings and description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly illustrative embodiments thereof have been shown and described andthat all changes and modifications that come within the spirit of theinvention are desired to be protected. For example, in some alternateembodiments, one or more conventional ion analytical instruments may besubstituted for either or both of the ion source 18 and the ion detector22 such that alternate and/or additional ion separation, ionconformation alteration, ion processing and/or ion analysis may becarried out on ions prior to entering and/or after exiting thesingle-pass drift tube 12, 12′, 12″, 12′″. Alternatively oradditionally, one or more conventional ion analytical instruments may bepositioned within or interposed along either or both of the single-passdrift tube 12, 12′, 12″, 12′″ and the multiple-pass drift tube 14, 14′,14″ such that alternate and/or additional ion separation, ionconformation alteration, ion processing and/or ion analysis may becarried out within or along the single-pass drift tube 12, 12′, 12″,12′″ and/or the multiple-pass drift tube 14, 14′, 14″. In any case,examples of such conventional ion analytical instruments that precedethe ion inlet 16 of the single-pass drift tube 12, 12′, 12″, 12′″, thatfollow the ion outlet 20 of the single-pass drift tube 12, 12′, 12″,12′″ and/or that are positioned within or interposed along thesingle-pass drift tube 12, 12′, 12″, 12′″ and/or the multiple-pass drifttube 14, 14′, 14″ may include, but are not limited to, one or more drifttubes identical to or different from the single-pass drift tube 12, 12′,12″, 12′″ and/or the multiple-pass drift tube 14, 14′, 14″, one or moremass analyzers and/or mass spectrometers, one or more liquid and/or gaschromatographs, one or mass filters (e.g., one or more multiple-polemass filters), one or more collision cells and/or other ionfragmentation devices or regions, one or more ion activation regions inwhich an electric field is established that is high enough to alter theconformation of one or more ions but not high enough to fragment ions,or the like. It will be further understood that in embodiments thatinclude two or more such conventional ion analytical instrumentstogether, such two or more conventional ion analytical instruments maybe positioned in parallel relative to each other, in series relative toeach other (i.e., cascaded) or any combination of series and parallel.

Additionally or alternatively, those skilled in the art will recognizethat the multiple-pass drift tube 14 illustrated in any of FIGS. 1A-1Bcan, in some embodiments, be provided in the form of two or moreseries-connected and/or parallel-connected multiple-pass drift tubes.Alternatively or additionally still, such one or more multiple-passdrift tubes 14 can be augmented by one or more single-pass drift tubes12 and/or by one or more conventional analytical instruments of the typedescribed by example in the previous paragraph.

As another example, it will be understood that while the variousembodiments of the hybrid ion mobility spectrometer 10, 10′, 10″, 10′″illustrated and described herein include a multiple-pass drift tube 14,14′, 14″ coupled to a single-pass drift tube 12, 12′, 12″, 12′″ betweenan ion inlet 16 and an ion outlet 20 of the single-pass drift tube 12,12′, 12″, 12′″, this disclosure contemplates alternative embodiments inwhich the multiple-pass drift tube 14, 14′, 14″ or other suitablemultiple-pass drift tube is positioned upstream of the single-pass drifttube 12, 12′, 12″, 12′″, i.e., prior to the ion inlet 16 and/ordownstream of the single-pass drift tube 12, 12′, 12″, 12′″, i.e.,following the ion outlet 20.

As still another example, operation of the ion gates G1-G3 or G1-G4 hasbeen described herein in which such ion gates G1-G3 or G1-G4 arecontrolled to block or allow passage therethrough of some or all ionsfrom a preceding, e.g. upstream, stage or section of the hybrid ionmobility spectrometer 10, 10′, 10″, 10′″. It will be understood thatthis disclosure contemplates embodiments in which any one or more of thegates G1-G3 or G1-G4 may be controlled to intermediate positions, i.e.,between their open and closed positions, to allow pass therethrough ofonly a fraction of the ions at any one or more times. This would allow,for example, operation of the single-pass drift tube 12, 12′, 12″, 12′″to be carried out simultaneously with the operation of the multiple-passdrift tube 14, 14′, 14″ such that ions exiting more quickly from thesingle-pass drift tube 12, 12′, 12″, 12′″ can be analyzed prior toanalyzing ions exiting the multiple-pass drift tube.

1. A hybrid ion mobility spectrometer comprising: a single-pass drift tube having an ion inlet at one end and an ion outlet at an opposite end, the single-pass drift tube configured to separate in time ions entering the ion inlet thereof and traveling therethrough according to a first function of ion mobility, a multiple-pass drift tube having an ion inlet and an ion outlet each coupled to the single pass drift tube between the ion inlet of the single-pass drift tube and the ion outlet of the single-pass drift tube, the multiple-pass drift tube configured to separate in time ions entering the ion inlet of the multiple-pass drift tube and traveling one or more times therethrough according to the first or a second function of ion mobility, and a set of ion gates each controllable between an open position to pass ions therethrough and a closed position to block ions from passing therethrough, the set of ion gates controlled between the open and closed positions to selectively pass at least some of the ions traveling through the single-pass drift tube into the multiple-pass drift tube via the ion inlet of the multiple-pass drift tube and to selectively pass at least some of the ions traveling through the multiple-pass drift tube into the single-pass drift tube via the ion outlet of the multiple-pass drift tube.
 2. The hybrid ion mobility spectrometer of claim 1 wherein each of the set of ions gates is controllable to the open position in response to a different first ion gate control signal and is controllable to the closed position in response to a different second ion gate control signal, and further comprising a first plurality of voltage sources to produce the different first and second ion gate control signals.
 3. The hybrid ion mobility spectrometer of claim 2 wherein one or more voltage sources within the first plurality of voltage sources is programmable to control timing of production of at least one of the different first ion gate control signals and at least one of the different second ion gate control signals.
 4. The hybrid ion mobility spectrometer of claim 2 further comprising a processor electrically coupled to at least one of the first plurality of voltage sources, the processor to control timing of production of at least one of the different first ion gate control signals and at least one of the different second ion gate control signals.
 5. The hybrid ion mobility spectrometer of claim 2 wherein the single-pass drift tube is responsive to a first set of voltage signals to separate ions in time according to the first function of ion mobility and the multiple-pass drift tube is responsive to a second set of voltage signals to separate ions in time according to the first or second function of ion mobility, and further comprising a second plurality of voltage sources to produce the first and second sets of voltage signals. 6.-7. (canceled)
 8. The hybrid ion mobility spectrometer of claim 1 wherein the set of ions gates define: a first combination of open and closed positions of the set of ion gates that directs ions to travel through the single-pass drift tube while blocking ions from entering the ion inlet of the multiple-pass drift tube, such that ions entering the ion inlet of the single-pass drift tube travel completely through the single-pass drift tube and exit the ion outlet thereof, a second combination of open and closed positions of the set of ion gates that directs at least some of the ions traveling through the single-pass drift tube into the ion inlet of the multiple-pass drift tube, a third combination of open and closed positions of the set of ion gates that directs ions in the multiple-pass drift tube to travel multiple times therethrough while blocking ions traveling through the multiple-pass drift tube from exiting the ion outlet thereof and re-entering the single-pass drift tube, and a fourth combination of open and closed positions of the set of ion gates that directs at least some of the ions traveling through the multiple-pass drift tube through the ion outlet thereof and into the single-pass drift tube, wherein ions entering the single-pass drift tube from the ion outlet of the multiple-pass drift tube travel toward and exit through the ion outlet of the single-pass drift tube.
 9. The hybrid ion mobility spectrometer of claim 1 wherein the multiple-pass drift tube comprises a closed-path drift tube, the ion inlet of the multiple-pass drift tube comprises an ion inlet tube having an ion outlet integrally formed with the multiple-pass drift tube and the ion outlet of the multiple-pass drift tube comprises an ion outlet tube having an ion inlet integrally formed with the multiple-pass drift tube.
 10. (canceled)
 11. The hybrid ion mobility spectrometer of claim 9 wherein the single-pass drift tube comprises a first plurality of cascaded drift tube segments, wherein the closed-path drift tube comprises a second plurality of cascaded drift tube segments with an ion outlet of a last one of the second plurality of cascaded drift tube segments coupled to an ion inlet of a first one of the second plurality of cascaded drift tube segments, and wherein at least one of the first plurality of drift tube segments and at least one of the second plurality of drift tube segments define at least one common drift tube segment. 12.-14. (canceled)
 15. The hybrid ion mobility spectrometer of claim 9 wherein the single-pass drift tube comprises a first plurality of linearly arranged, cascaded drift tube segments, wherein the closed-path drift tube comprises a second plurality of cascaded drift tube segments with an ion outlet of a last one of the second plurality of cascaded drift tube segments coupled to an ion inlet of a first one of the second plurality of cascaded drift tube segments, and wherein the ion inlet of the multiple-pass drift tube is coupled to one of the first plurality of drift tube segments and the ion outlet of the multiple-pass drift tube is coupled to another of the first plurality of drift tube segments downstream of the one of the first plurality of drift tube segments. 16.-18. (canceled)
 19. The hybrid ion mobility spectrometer of claim 1 wherein the single-pass drift tube comprises a first plurality of linearly arranged, cascaded drift tube segments, wherein the multiple-pass drift tube comprises a closed-path drift tube, the closed-path drift tube comprising a second plurality of cascaded drift tube segments with an ion outlet of a last one of the second plurality of cascaded drift tube segments coupled to an ion inlet of a first one of the second plurality of cascaded drift tube segments, and wherein the ion inlet and the ion outlet of the multiple-pass drift tube together comprise an ion inlet-outlet tube coupled at one end to one of the first plurality of drift tube segments between the ion inlet of the single-pass drift tube and the ion outlet of the single-pass drift tube and at an opposite end to one of the second plurality of drift tube segments. 20.-21. (canceled)
 22. The hybrid ion mobility spectrometer of claim 1 further comprising an ion source coupled to the ion inlet of the single-pass drift tube, the ion source configured to generate ions from a sample.
 23. The hybrid ion mobility spectrometer of claim 1 further comprising an ion detector to detect ions exiting the ion outlet of the single-pass drift tube and to produce an ion detection signal corresponding thereto.
 24. The hybrid ion mobility spectrometer of claim 23 further comprising a processor to process the ion detection signal and produce corresponding ion mobility spectral information as a function of ion drift time.
 25. The hybrid ion mobility spectrometer of claim 1 wherein each of the set of ion gates is controllable to at least one intermediate position to pass at least some ions therethrough, one or more of the set of ion gates controlled to the at least one intermediate position to selectively pass some of the ions traveling through the single-pass drift tube into the multiple-pass drift tube while also allowing others of the ions traveling through the single-pass drift to travel through the single-pass drift tube to the outlet thereof.
 26. A method for separating ions comprising: introducing ions into an ion inlet of a first drift tube, establishing at least a first electric field within the first drift tube to cause at least some of the ions introduced into the ion inlet thereof to travel through the first drift tube from the ion inlet thereof toward an ion outlet thereof while separating in time according to a first function of ion mobility, controlling a set of ion gates to direct at least some of the ions traveling through the first drift tube into a second drift tube via an ion inlet of the second drift tube that is coupled to the first drift tube between the ion inlet of the first drift tube and the ion outlet of the first drift tube, establishing at least a second electric field within the second drift tube to cause ions entering the ion inlet thereof to travel through the second drift tube while separating in time according to the first or a second function of ion mobility, controlling the set of ion gates to cause ions traveling through the second drift tube to travel through the second drift tube multiple times, and controlling the set of ion gates to direct at least some of the ions having traveled the multiple times through the second drift tube into the first drift tube via an ion outlet of the second drift tube that is coupled to the first drift tube between the ion inlet of the first drift tube and the ion outlet of the first drift tube, wherein at least some of the ions passing into the first drift tube from the ion outlet of the second drift tube travel toward and exit through the ion outlet of the first drift tube.
 27. The method of claim 26 wherein introducing ions into the ion inlet of the first drift tube comprises introducing a first set of ions into the ion inlet of the first drift tube, and further comprising: controlling the set of ion gates to cause the first set of ions to travel through the first drift tube and exit through the ion outlet of the first drift tube, determining, based on the first set of ions exiting the ion outlet of the first drift tube, a range of ion mobilities of at least some of the first set of ions, and introducing a second set of ions into the ion inlet of the first drift tube after introducing the first set of ions into the ion inlet of the first drift tube, wherein controlling the set of ion gates to direct at least some of the ions traveling through the first drift tube into the second drift tube comprises controlling the set of ion gates to direct the second set of ions traveling through first drift tube into the second drift tube via the ion inlet of the second drift tube, and further comprising controlling the second electric field to cause only ions in the second set of ions that are within the determined range of ion mobilities to travel through the second drift tube, wherein controlling the set of ion gates to direct at least some of the ions having traveled the multiple times through the second drift tube into the first drift tube comprises controlling the set of ion gates to direct ions from the second set of ions that are traveling through the second drift tube into the first drift tube via the ion outlet of the second drift tube, and wherein the ions from the second set of ions passing into the first drift tube from the ion outlet of the second drift tube exit through the ion outlet of the first drift tube and have ion mobilities only within the defined range of ion mobilities.
 28. The method of claim 27 further comprising generating the first and second sets of ions from a common sample.
 29. (canceled)
 30. The method of claim 26 wherein the second drift tube defines a closed path, the ion inlet of the second drift tube comprises an ion inlet tube integrally formed with the second drift tube and the ion outlet of the second drift tube comprises an ion outlet tube also integrally formed with the second drift tube, and wherein controlling the set of ion gates to cause ions traveling through the second drift tube to travel through the second drift tube multiple times comprises controlling the set of ion gates to block the ions traveling through the second drift tube from exiting the second drift tube via the ion outlet of the second drift tube and to direct the ions traveling through the second drift tube to travel multiple times about the closed path.
 31. The method of claim 26 wherein one or more of the steps of controlling the set of ion gates comprises controlling the set of ion gates using a processor.
 32. The method of claim 26 further comprising an ion detector to detect ions exiting the ion outlet of the first drift tube and produce an ion detection signal corresponding thereto, and wherein the method further comprises: generating ions prior to introducing the ions into the ion inlet of the first drift tube, and processing the ion detection signal to produce ion mobility spectral information as a function of ion drift time. 33.-60. (canceled) 